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HODGKIN LYMPHOMA IN CHILDREN Dr.M.Shamvil Ashraf Children Cancer Hospital, Karachi.

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Presentation on theme: "HODGKIN LYMPHOMA IN CHILDREN Dr.M.Shamvil Ashraf Children Cancer Hospital, Karachi."— Presentation transcript:

1 HODGKIN LYMPHOMA IN CHILDREN Dr.M.Shamvil Ashraf Children Cancer Hospital, Karachi.

2 Hodgkin Lymphoma One of the most curable cancer in children One of the most curable cancer in children There are different effective treatment approaches There are different effective treatment approaches Can be cured with limited resources Can be cured with limited resources

3 Epidemiology Developed Countries 5 - 6% of childhood cancers 5 - 6% of childhood cancers Male:Female 3-4:1 in <10y Male:Female 3-4:1 in <10y Male:Female 1.3:1 in >10y Male:Female 1.3:1 in >10y Bimodal age peak- adolescent/young adult, 50yo Bimodal age peak- adolescent/young adult, 50yo Uncommon in <10 yrs Uncommon in <10 yrs Karachi Data 10% of childhood cancers 10% of childhood cancers Male:Female 4.7:1 in <10y Male:Female 4.7:1 in <10y Male:Female 1.7:1 in >10y Male:Female 1.7:1 in >10y > 5 years 24% > 5 years 24% >10years 62% >10years 62%

4 Biology Inflammatory milieu with rare multinucleated giant cells (Reed-Sternberg cells) or large mononuclear cell variants (Hodgkins or lacunar cells) Inflammatory milieu with rare multinucleated giant cells (Reed-Sternberg cells) or large mononuclear cell variants (Hodgkins or lacunar cells) R-S cell appears to arise from preapoptotic germinal center B cells (no Ig production), although rarely may arise from T cells R-S cell appears to arise from preapoptotic germinal center B cells (no Ig production), although rarely may arise from T cells

5 RS cells

6 Lacunar Cells

7 Cellular Classification Classical HL (CD15, CD30 +, B cell markers ) Classical HL (CD15, CD30 +, B cell markers ) nodular sclerosis (50-60%) nodular sclerosis (50-60%) mixed-cellularity (20-30%) mixed-cellularity (20-30%) lymphocyte rich (<5%) lymphocyte rich (<5%) lymphocyte depleted (5-15%) lymphocyte depleted (5-15%) Nodular Lymphocyte Predominant HL (5%) (CD15 -, CD30 +/-, B cell markers +) Nodular Lymphocyte Predominant HL (5%) (CD15 -, CD30 +/-, B cell markers +)

8 44 (55%) 21 (26%) 2 (2.5%) 13 (16.2%) Pathological Subtypes; Karachi Data

9 Clinical Presentation Painless adenopathy (80%) Painless adenopathy (80%) B symptoms (25-30%) B symptoms (25-30%) fever >38 0 C x 3 days fever >38 0 C x 3 days wt loss >10% of body wt. over 6 mo wt loss >10% of body wt. over 6 mo drenching night sweats drenching night sweats Bulky disease (20%) Bulky disease (20%) med mass >1/3 of internal thoracic diameter med mass >1/3 of internal thoracic diameter node/nodal aggregate >6 cm node/nodal aggregate >6 cm

10 Clinical Presentation 15% to 20% of patients will have noncontiguous extranodal involvement 15% to 20% of patients will have noncontiguous extranodal involvement The most common sites of extranodal involvement are the lung, liver, bones, and bone marrow The most common sites of extranodal involvement are the lung, liver, bones, and bone marrow

11 Hodgkin vs TB Most common differential especially if limited to cervical Most common differential especially if limited to cervical Often put on ATT without definitive diagnosis Often put on ATT without definitive diagnosis Biopsy is essential Biopsy is essential

12 Diagnosis Excision Biopsy of Node Excision Biopsy of Node Needle Biopsy of mass if excision not possible Needle Biopsy of mass if excision not possible FNAC is not recommended in children FNAC is not recommended in children

13 Staging Ann Arbor staging system I-IV Ann Arbor staging system I-IV A vs B A vs B E- extralymphatic disease resulting from direct extension of involved LN region E- extralymphatic disease resulting from direct extension of involved LN region S- splenic disease S- splenic disease ideally want pathologic confirmation of noncontiguous extralymphatic involvement (Stage IV disease) ideally want pathologic confirmation of noncontiguous extralymphatic involvement (Stage IV disease)

14 Ann Arbor Staging Stage I: Involvement of single lymph node region (I) or localized involvement of a single extralymphatic organ or site (I E ) Stage I: Involvement of single lymph node region (I) or localized involvement of a single extralymphatic organ or site (I E ) Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single extralymphatic organ or site and its regional lymph node(s) with involvement of one or more lymph regions on the same side of the diaphragm (II E ) Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single extralymphatic organ or site and its regional lymph node(s) with involvement of one or more lymph regions on the same side of the diaphragm (II E ) Stage III: Involvement of lymph node regions on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an extralymphatic organ or site (III E ), by involvement of the spleen (II S ), or both (III E+S ) Stage III: Involvement of lymph node regions on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an extralymphatic organ or site (III E ), by involvement of the spleen (II S ), or both (III E+S ) Stage IV: Disseminated (multifocal) involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement, or isolated extralymphatic organ involvement with distant (non-regional) nodal involvement. Stage IV: Disseminated (multifocal) involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement, or isolated extralymphatic organ involvement with distant (non-regional) nodal involvement.

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16 Staging Workup Imaging CXR CXR U/Sound U/Sound CT scan of neck, chest, abdomen and pelvis CT scan of neck, chest, abdomen and pelvis Gallium Gallium PET Scan PET Scan Other Tests Bone marrow aspirate and trephine only in Bone marrow aspirate and trephine only in Patients with stage II B or more Patients with stage II B or more Bone scan only in stage III or more Bone scan only in stage III or more Blood tests Blood tests CBC CBC LDH LDH Urea, Cr, electrolytes, Ca, Mg, LFTs Urea, Cr, electrolytes, Ca, Mg, LFTs Hepatitis screening Hepatitis screening

17 Therapy: History XRT alone cured early stage disease 1960s- MOPP 1970s- ABVD Combined modality therapy (CMT) Chemotherapy and radiation

18 Therapy History Good results were obtained but at the cost of severe late toxicities Good results were obtained but at the cost of severe late toxicities XRT ; profound musculoskeletal growth retardation and increase the risk for cardiovascular disease and secondary solid malignancies in children XRT ; profound musculoskeletal growth retardation and increase the risk for cardiovascular disease and secondary solid malignancies in children Chemotherapy induced gonadal injury,cardiovascular disease and SMN Chemotherapy induced gonadal injury,cardiovascular disease and SMN

19 Combination Chemotherapy Regimens Commonly Used for Children and Young Adults with Hodgkin Lymphoma ABVD doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine ABVE doxorubicin (Adriamycin), bleomycin, vincristine, etoposide VAMP vincristine, doxorubicin (Adriamycin), methotrexate, prednisone OPPA +/- COPP vincristine, prednisone, procarbazine, doxorubicin, cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine COPP/ABV cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine, doxorubicin (Adriamycin), bleomycin, vinblastine BEACOPP bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine

20 Hodgkins Therapy in 90`s Prognostic factors and risk grouping concept introduced Prognostic factors and risk grouping concept introduced Radiation dose and field were reduced Radiation dose and field were reduced Involved Field Radiotherapy introduced Involved Field Radiotherapy introduced Chemotherapy regimen were manipulated Chemotherapy regimen were manipulated to reduce cumulative dose and avoid long term toxicities to reduce cumulative dose and avoid long term toxicities

21 Determining Risk Assignment I

22 Chemotherapy Options

23 Current Approaches Current approaches use chemotherapy with or without LD-IFRT Current approaches use chemotherapy with or without LD-IFRT An exception to this general approach is selected patients with stage I, completely resected, nodular lymphocyte-predominant Hodgkin lymphoma, whose initial treatment may be surgery alone. An exception to this general approach is selected patients with stage I, completely resected, nodular lymphocyte-predominant Hodgkin lymphoma, whose initial treatment may be surgery alone. The number of cycles and intensity of chemotherapy may be determined by the rapidity and degree of response, as is the radiation dose and volume. The number of cycles and intensity of chemotherapy may be determined by the rapidity and degree of response, as is the radiation dose and volume.

24 Approach for Developing Countries Chemotherapy Alone Chemotherapy Alone If radiotherapy is not available If radiotherapy is not available Pediatric radiotherapy service is not developed Pediatric radiotherapy service is not developed Good result (up to 80% survival) can be obtained as shown by Indian Experience Good result (up to 80% survival) can be obtained as shown by Indian Experience (Arya et al) (Arya et al)

25 Approach for Developing Countries Chemotherapy with Radiotherapy only for bulky residual disease Chemotherapy with Radiotherapy only for bulky residual disease Excellent result can be achieved with this approach as shown by our experience at Children Cancer Hospital Excellent result can be achieved with this approach as shown by our experience at Children Cancer Hospital

26 CCH Data Retrospective study Retrospective study From Aug All the patients with histopathological diagnosis of Hodgkin Lymphoma, up to 20 years of age were included From Aug All the patients with histopathological diagnosis of Hodgkin Lymphoma, up to 20 years of age were included Mean age: 9.9 yrs Mean age: 9.9 yrs Pts. included in the study – 80 Pts. included in the study – 80

27 Treatment Strategy At CCH Chemotherapy used was alternating courses of Chemotherapy used was alternating courses of ABVD (adriamycin, bleomycin, vincristine and dacarbazine) ABVD (adriamycin, bleomycin, vincristine and dacarbazine) COPDAC (cyclophophamide, vincristine, prednisolone and dacarbazine) COPDAC (cyclophophamide, vincristine, prednisolone and dacarbazine) Radiotherapy was reserved only for the pts. with significant residual disease at the end of chemotherapy Radiotherapy was reserved only for the pts. with significant residual disease at the end of chemotherapy

28 Response Assessment CT scan of all the sites positive on pre treatment scan was repeated after 2 cycles CT scan of all the sites positive on pre treatment scan was repeated after 2 cycles Bone marrow or bone scan was repeated only if it was positive initially Bone marrow or bone scan was repeated only if it was positive initially For good responder CT was repeated after 6 cycles For good responder CT was repeated after 6 cycles PET scan could not be performed because of non-availability PET scan could not be performed because of non-availability

29 Response Assessment Criteria CR was taken as complete resolution of all measurable disease, clinically and radiologically CR was taken as complete resolution of all measurable disease, clinically and radiologically >80% response was taken as good response >80% response was taken as good response 60 to 80% was taken as partial response 60 to 80% was taken as partial response <60% was taken as poor response or stable disease <60% was taken as poor response or stable disease Any increase in the size of an existing lesion or appearance of any new lesion during treatment was taken as progressive disease Any increase in the size of an existing lesion or appearance of any new lesion during treatment was taken as progressive disease

30 Response Adapted Therapy Low risk patients with CR after 2 courses received 4 courses Low risk patients with CR after 2 courses received 4 courses All other pts were given 6 – 8 courses depending upon the response (CR + 2 courses) All other pts were given 6 – 8 courses depending upon the response (CR + 2 courses) 11(13.7%) pts received 4 courses 11(13.7%) pts received 4 courses Majority of pts 56 (70%) received 6 courses Majority of pts 56 (70%) received 6 courses

31 Radiation Therapy Radiation therapy was reserved only for the pts with residual disease at the end of chemo Radiation therapy was reserved only for the pts with residual disease at the end of chemo only 8 (10%) needed radiation only 8 (10%) needed radiation Stage II A – 1 pt Stage II A – 1 pt Stage II B – 1 pt Stage II B – 1 pt Stage III B – 3 pts Stage III B – 3 pts Stage III BS – 1 pt Stage III BS – 1 pt Stage IV – 2 pts Stage IV – 2 pts

32 Results 74 (92%) pts achieved first remission (CR) after 2 courses of chemotherapy 74 (92%) pts achieved first remission (CR) after 2 courses of chemotherapy Only one pt. died during chemotherapy due to meningitis Only one pt. died during chemotherapy due to meningitis One pt. relapsed on treatment and was switched to second line treatment One pt. relapsed on treatment and was switched to second line treatment 4 (5%) pts relapsed 2 – 12 months after completion of chemotherapy 4 (5%) pts relapsed 2 – 12 months after completion of chemotherapy 3 yrs OS 98% and EFS 92% 3 yrs OS 98% and EFS 92%

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34 Progressive/Relapsed Ds Prognostic factors: –progressive ds or relapse at <1y from end of treatment –B symptoms –extranodal ds –response to salvage therapy

35 Chemotherapy Options Salvage therapies (with harvest) Salvage therapies (with harvest) ICE, EPIC,mini-BEAM, DHAP, ASHAP, bortezomib/ifos/vinorelbine (AHOD 0521), GDP (PMH) ICE, EPIC,mini-BEAM, DHAP, ASHAP, bortezomib/ifos/vinorelbine (AHOD 0521), GDP (PMH) Autologous transplant Autologous transplant conditioning: CBV, BEAM, VP16/melphalan conditioning: CBV, BEAM, VP16/melphalan BEAM plus immunomodulation (AHOD 0121)- closed BEAM plus immunomodulation (AHOD 0121)- closed

36 Refractory Disease Gemcitabine/Vinorelbine AHOD closed –eligibility: >/= 2 prior regimens –beware non-cardiogenic pulmonary edema –may require 4-6 cycles to see response Vinblastine, lomustine, VP16 New agents/targeted therapies

37 Late Effects Cardiotoxicity and Musculoskeletal problems are now rare Cardiotoxicity and Musculoskeletal problems are now rare Endocrine Endocrine Thyroid ; Hypothyroidism Thyroid ; Hypothyroidism Fertility; Fertility; Increased risk of ovarian failure in women Increased risk of ovarian failure in women Oligospermia and sterility in men Oligospermia and sterility in men Second Malignant Neoplasm Second Malignant Neoplasm

38 Conclusion Chemotherapy alone in majority of patients with Hodgkin Lymphoma can yield excellent outcome Chemotherapy alone in majority of patients with Hodgkin Lymphoma can yield excellent outcome Most of Hodgkin Disease pts can be managed without the use of radiotherapy, thereby minimizing the adversity associated with radiation, specially in young children Most of Hodgkin Disease pts can be managed without the use of radiotherapy, thereby minimizing the adversity associated with radiation, specially in young children Hodgkin Lymphoma can be cured within limited resources Hodgkin Lymphoma can be cured within limited resources Monitoring for late effects is important Monitoring for late effects is important


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